Scapholunate ligaments (SLLs) play a well-established role in maintaining carpal alignment and kinematics, and are innervated with sensory mechanoreceptors located within the ligaments. They are ...involved in the afferent arc of dynamic wrist stability. The aim of this study was to describe the changes in these mechanoreceptor populations in injured SLLs.
Injured SLLs were collected from human wrists at the time of SLL reconstruction or limited wrist fusion, where the ligament remnants would otherwise be discarded. These specimens were formalin-fixed and paraffin-embedded for immunohistochemical analysis to identify mechanoreceptors, which were then classified by type and location within the ligament.
A total of 15 ligaments were collected, with the interval from injury ranging from 39 days-20 years. Eleven ligaments were collected less than one year after injury, and four ligaments were collected two years or more after injury. A total of 66 mechanoreceptors were identified, with 50 mechanoreceptors identified in nine of the 11 specimens collected less than one year after injury. In this group, 54% of the mechanoreceptors resided in the volar subunit, 20% in the dorsal subunit, and 26% in the proximal subunit. Two of the four specimens collected two years or later after injury contained mechanoreceptors, all of which were located in the dorsal subunit. Increasing time from injury demonstrated a decline in mechanoreceptor numbers within the volar subunit.
Mechanoreceptors were consistently located in the SLL, particularly in the volar subunit of specimens collected less than one year after injury.
Ligament reconstruction techniques aim to primarily reconstitute the biomechanical function of the disrupted SLL; however, re-establishing the afferent proprioceptive capacity of the SLL may be a secondary objective. This suggests the need to consider the reconstruction of its volar subunit particularly in those managed within one year of injury.
In addition to being a prerequisite for many activities of daily living, the ability to maintain steady upright standing is a relevant model to study sensorimotor integrative function. Upright ...standing requires managing multimodal sensory inputs to produce finely tuned motor output that can be adjusted to accommodate changes in standing conditions and environment. The sensory information used for postural control mainly arises from the vestibular system of the inner ear, vision, and proprioception. Proprioception (sense of body position and movement) encompasses signals from mechanoreceptors (proprioceptors) located in muscles, tendons, and joint capsules. There is general agreement that proprioception signals from leg muscles provide the primary source of information for postural control. This is because of their exquisite sensitivity to detect body sway during unperturbed upright standing that mainly results from variations in leg muscle length induced by rotations around the ankle joint. However, aging is associated with alterations of muscle spindles and their neural pathways, which induce a decrease in the sensitivity, acuity, and integration of the proprioceptive signal. These alterations promote changes in postural control that reduce its efficiency and thereby may have deleterious consequences for the functional independence of an individual. This narrative review provides an overview of how aging alters the proprioceptive signal from the legs and presents compelling evidence that these changes modify the neural control of upright standing.
Research has shown that psychedelics, such as lysergic acid diethylamide (LSD), have profound anti-inflammatory properties mediated by 5-HT
2A
receptor signaling, supporting their evaluation as a ...therapeutic for neuroinflammation associated with neurodegenerative disease.
Objective
This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of orally repeated administration of 5 μg, 10 μg, and 20 μg LSD in older healthy individuals. In the current paper, we present safety, tolerability, pharmacokinetics, and pharmacodynamic measures that relate to safety, tolerability, and dose response.
Methods
This was a phase 1 double-blind, placebo-controlled, randomized study. Volunteers were randomly assigned to 1 of 4 dose groups (5 μg, 10 μg, 20 μg LSD, and placebo), and received their assigned dose on six occasions (i.e., every 4 days).
Results
Forty-eight older healthy volunteers (mean age = 62.9 years) received placebo (
n
= 12), 5 μg (
n
= 12), 10 μg (
n
= 12), or 20 μg (
n
= 12) LSD. LSD plasma levels were undetectable for the 5 μg group and peak blood plasma levels for the 10 μg and 20 μg groups occurred at 30 min. LSD was well tolerated, and the frequency of adverse events was no higher than for placebo. Assessments of cognition, balance, and proprioception revealed no impairment.
Conclusions
Our results suggest safety and tolerability of orally administered 5 μg, 10 μg, and 20 μg LSD every fourth day over a 21-day period and support further clinical development of LSD for the treatment and prevention of Alzheimer’s disease (AD).
Proprioception, the perception of body and limb position, is mediated by proprioceptors, specialized mechanosensory neurons that convey information about the stretch and tension experienced by ...muscles, tendons, skin and joints. In mammals, the molecular identity of the stretch-sensitive channel that mediates proprioception is unknown. We found that the mechanically activated nonselective cation channel Piezo2 was expressed in sensory endings of proprioceptors innervating muscle spindles and Golgi tendon organs in mice. Two independent mouse lines that lack Piezo2 in proprioceptive neurons showed severely uncoordinated body movements and abnormal limb positions. Moreover, the mechanosensitivity of parvalbumin-expressing neurons that predominantly mark proprioceptors was dependent on Piezo2 expression in vitro, and the stretch-induced firing of proprioceptors in muscle-nerve recordings was markedly reduced in Piezo2-deficient mice. Together, our results indicate that Piezo2 is the major mechanotransducer of mammalian proprioceptors.
Motor neurons are the final common pathway
through which the brain controls movement of the body, forming the basic elements from which all movement is composed. Yet how a single motor neuron ...contributes to control during natural movement remains unclear. Here we anatomically and functionally characterize the individual roles of the motor neurons that control head movement in the fly, Drosophila melanogaster. Counterintuitively, we find that activity in a single motor neuron rotates the head in different directions, depending on the starting posture of the head, such that the head converges towards a pose determined by the identity of the stimulated motor neuron. A feedback model predicts that this convergent behaviour results from motor neuron drive interacting with proprioceptive feedback. We identify and genetically
suppress a single class of proprioceptive neuron
that changes the motor neuron-induced convergence as predicted by the feedback model. These data suggest a framework for how the brain controls movements: instead of directly generating movement in a given direction by activating a fixed set of motor neurons, the brain controls movements by adding bias to a continuing proprioceptive-motor loop.
The sensation of pressure allows us to feel sustained compression and body strain. While our understanding of cutaneous touch has grown significantly in recent years, how deep tissue sensations are ...detected remains less clear. Here, we use quantitative sensory evaluations of patients with rare sensory disorders, as well as nerve blocks in typical individuals, to probe the neural and genetic mechanisms for detecting non-painful pressure. We show that the ability to perceive innocuous pressures is lost when myelinated fiber function is experimentally blocked in healthy volunteers and that two patients lacking Aβ fibers are strikingly unable to feel innocuous pressures at all. We find that seven individuals with inherited mutations in the mechanoreceptor PIEZO2 gene, who have major deficits in touch and proprioception, are nearly as good at sensing pressure as healthy control subjects. Together, these data support a role for Aβ afferents in pressure sensation and suggest the existence of an unknown molecular pathway for its detection.
Proprioceptive information from the hips, knees, and ankles as well as joint coordination are important for maintaining and controlling balance. Regional receptors in the muscles, joints, skin, and ...tendons as well as proprioception in the knee joint provide the necessary joint activity and stability. Pain may occur with a decreased sense of balance and proprioception.
To investigate the relationship between single-leg balance and proprioception of the knee joint in individuals with non-specific chronic low back pain.
Fifty-two individuals with non-specific chronic low back pain, 30 females and 22 males, were included in our study, with a range of 18–50 years (mean age:25.15 ± 8.2 years).
Pain intensity at rest and activity was assessed using Visual Analogue Scale (VAS), and disability and function were assessed using Oswestry Disability Index (ODI). Single-leg balance measurements were performed using Prokin TecnoBody kinematic balance device. A goniometer was used to evaluate the proprioception of the knee joint.
There were low-level negative correlations between VAS resting pain intensity and medium-lateral standard deviation value (p = 0.018; r = −0.327) and ellipse area measure (p = 0.039; r = −0.287) from static balance assessments. There were low-level negative correlations between VAS activity pain intensity and medium-lateral standard deviation value (p = 0.039; r = −0.288), ellipse area (p = 0.044; r = −0.281), and perimeter measure (p = 0.043; r = −0.282) from static balance assessments. No correlation was seen between ODI and clinical balance and proprioception assessments (p > 0.05). There was no correlation between clinical balance and proprioception evaluations (p > 0.05).
As a result of the study, it was decided that there is a minimal relationship between single-leg balance and knee joint proprioception in people with nonspecific low back pain.
To compare subjects' sensory responses to horizontal and vertical forces on tooth- and implant-supported restorations.
In this prospective study, three protocols simulating the horizontal or vertical ...forces that occur during mastication were used to obtain subjective responses from subjects. These protocols included the measurement of horizontal force intensity during excursive movements and the identification of initial contact during guided and free vertical closure. Responses were recorded using a 1- to 10-point visual analog scale (VAS) and/ or monitored with electromyography (EMG) and Tekscan.
The study included 30 patients with a single implant-supported restoration (ISR) with a contralateral tooth-supported restoration (TSR). For horizontal forces similar to those of mastication (0.6 N), subject VAS scores were similar for both ISRs and TSRs at 6.3 vs 6.1, respectively. At reduced forces (0.2 and 0.4 N), subject responses were greater for the TSR at 3.4 and 5.4, respectively, as opposed to 1.2 and 2.6 for ISR, respectively (
< .01). During vertical guided closure (Test 1) at 25% of maximum bite force (MBF), subjects were more successful at correctly identifying initial contact of TSRs at a rate of 12 out of 17, compared to ISRs, which achieved a rate of 4 out of 13 (
< .1). In vertical free closure (Test 2), subject responses for the correct identification of initial contact at 50% MBF were similar for both TSRs and ISRs at 13 out of 17 and 9 out of 13, respectively. However, comparing the correct responses for subjects whose initial contacts were ISR showed a significant improvement in correct answers from Test 1 to Test 2, from 4 out of 13 correct to 9 out of 13 correct (
< .05).
While the mechanism is not clear, subjects' ability to discern the horizontal and vertical forces at levels comparable to mastication appear similar between TSRs and ISRs.
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